PAIN®最新文献

{"title":"Na V 1.8/Na V 1.9 double deletion mildly affects acute pain responses in mice.","authors":"Marta Alves-Simões, Laura Teege, Cecilia Tomni, Martha Lürkens, Annika Schmidt, Federico Iseppon, Queensta Millet, Samuel Kühs, Istvan Katona, Joachim Weis, Stefan H Heinemann, Christian A Hübner, John Wood, Enrico Leipold, Ingo Kurth, Natja Haag","doi":"10.1097/j.pain.0000000000003411","DOIUrl":"10.1097/j.pain.0000000000003411","url":null,"abstract":"<p><strong>Abstract: </strong>The 2 tetrodotoxin-resistant (TTXr) voltage-gated sodium channel subtypes Na V 1.8 and Na V 1.9 are important for peripheral pain signaling. As determinants of sensory neuron excitability, they are essential for the initial transduction of sensory stimuli, the electrogenesis of the action potential, and the release of neurotransmitters from sensory neuron terminals. Na V 1.8 and Na V 1.9, which are encoded by SCN10A and SCN11A , respectively, are predominantly expressed in pain-sensitive (nociceptive) neurons localized in the dorsal root ganglia (DRG) along the spinal cord and in the trigeminal ganglia. Mutations in these genes cause various pain disorders in humans. Gain-of-function missense variants in SCN10A result in small fiber neuropathy, while distinct SCN11A mutations cause, i. a., congenital insensitivity to pain, episodic pain, painful neuropathy, and cold-induced pain. To determine the impact of loss-of-function of both channels, we generated Na V 1.8/Na V 1.9 double knockout (DKO) mice using clustered regularly interspaced short palindromic repeats/Cas-mediated gene editing to achieve simultaneous gene disruption. Successful knockout of both channels was verified by whole-cell recordings demonstrating the absence of Na V 1.8- and Na V 1.9-mediated Na + currents in Na V 1.8/Na V 1.9 DKO DRG neurons. Global RNA sequencing identified significant deregulation of C-LTMR marker genes as well as of pain-modulating neuropeptides in Na V 1.8/Na V 1.9 DKO DRG neurons, which fits to the overall only moderately impaired acute pain behavior observed in DKO mice. Besides addressing the function of both sodium channels in pain perception, we further demonstrate that the null-background is a very valuable tool for investigations on the functional properties of individual human disease-causing variants in Na V 1.8 or Na V 1.9 in their native physiological environment.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"773-792"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differences in the clinical presentation of chronic whiplash-associated disorders and nontraumatic neck pain: a systematic review and meta-analysis.","authors":"Junze Chen, Scott F Farrell, Wanyun Irene Huang, Barbara Cagnie, Carlos Murillo, Michele Sterling","doi":"10.1097/j.pain.0000000000003554","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003554","url":null,"abstract":"<p><strong>Abstract: </strong>Health outcomes may be worse for individuals with whiplash-associated disorders (WAD) compared to nontraumatic neck pain (NTNP), and clinical characteristics may differ. This systematic review examined evidence comparing WAD and NTNP in terms of pain, disability, psychological status, quality of life, measures of nociceptive processing, movement, sensorimotor, and muscle function. Studies were identified through electronic database searches and included after screening against predefined eligibility criteria. Standardized mean differences (SMD) or mean differences (MD) and 95% confidence intervals (CI) were calculated. Associations between MDs with demographics and study characteristics were explored using meta-regression. Certainty of evidence was assessed using Grades of Recommendation, Assessment, Development, and Evaluation. Sixty-one studies were eligible with 45 included in meta-analysis. Individuals with WAD reported clinically relevant higher disability (100-point Neck Disability Index MD [95% CI] 11.15 [8.63, 13.68]), greater remote cold sensitivity (SMD 0.89 [0.57, 1.21]), lower quality of life (SMD -0.96 [-1.77, -0.16]), greater depression (SMD 0.60 [0.27, 0.93]), greater local (SMD -0.56 [-1.00, -0.13]) and remote (SMD -0.50 [-0.81, -0.19]) pressure sensitivity, less cervical flexion (MD -5.30° [-7.44, -3.16]) and extension (MD -5.43° [-9.31, -1.55]), higher pain intensity (100-point numerical rating scale: MD 8.15 [5.80, 10.50]), and greater kinesiophobia (SMD 0.35 [0.11, 0.59]). No between-group differences were found for dizziness symptoms, stress, anxiety, balance, and local cold sensitivity. Meta-regression indicated that disability differences were negatively associated with age (R2 = 29.6%, P = 0.006). Certainty of evidence was mostly moderate. Individuals with chronic WAD have a worse clinical presentation compared to those with chronic NTNP, which has implications for patient assessment and management.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPV1 is the burner.","authors":"Annekathrin Alpes, Sofia Malek, Ralf Baron","doi":"10.1097/j.pain.0000000000003542","DOIUrl":"10.1097/j.pain.0000000000003542","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"717-718"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic pain in European adult populations: a systematic review of prevalence and associated clinical features.","authors":"Caroline Rometsch, Alexandra Martin, Florian Junne, Fiammetta Cosci","doi":"10.1097/j.pain.0000000000003406","DOIUrl":"10.1097/j.pain.0000000000003406","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic pain (CP) is a multifaceted and severely disabling persistent condition that affects individuals worldwide. A synthesis of epidemiological data is still lacking. The present systematic review aims at presenting point, period, and lifetime prevalence estimates of CP in the European adult population, as well as relevant features associated with it. Following PRISMA guidelines, a systematic search in PubMed, Web of Science, Embase, and Cochrane library was run from inception to May 2024, resulting in 39,832 hits. Among those, 132 full-text articles were assessed, and 23 studies comprising 862,013 participants with CP were included. The Joanna Biggs Institutes' Critical Appraisal Checklist for Studies Reporting Prevalence Data (JBI) was used for quality assessment. Findings showed a point prevalence ranging from 12% to 48%, a 6-month prevalence of 17.5% to 49.8%, a 12-month prevalence ranging from 8.1% to 44.6%, and a lifetime prevalence ranging from 12.7% to 33.7% independently from sex. Sociodemographic factors (eg, female sex, higher age, no partnership, lower education, unemployment) and clinical features (eg, medical diseases, mental disorders and burdens, healthcare utilization, functional impairment) were identified as being associated with CP. The variability in prevalence estimates can be reduced by applying consistent diagnostic criteria (eg, ICD-11) and by using standardized assessment tools (eg, scales, clinical interview). The high prevalence and the characteristics of the associated features support the need for adequate, multicomponent care paths to manage CP based on a comprehensive biopsychosocial model.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"166 4","pages":"719-731"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11921450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A revisit of soreness and acidosis-related pain.","authors":"I-Wen Su, Chih-Hsien Hung, Jiann-Her Lin, Chih-Cheng Chen","doi":"10.1097/j.pain.0000000000003595","DOIUrl":"https://doi.org/10.1097/j.pain.0000000000003595","url":null,"abstract":"","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":""},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trigeminal neuralgia and its comorbidities: a nationwide disease trajectory study.","authors":"Jacob Worm, Isabella Friis Jørgensen, Ólafur Birgir Davídsson, Henrik Hjalgrim, Timo Röder, Sisse Rye Ostrowski, Ole Birger Pedersen, Christian Erikstrup, Mie Topholm Bruun, Bitten Aagaard Jensen, Erik Sørensen, Henrik Ullum, Gyða Björnsdóttir, Thorgeir Thorgeirsson, Hreinn Stefánsson, Ólafur Árni Sveinsson, Kári Stefánsson, Henrik Winther Schytz, Lars Bendtsen, Søren Brunak, Thomas Folkmann Hansen, Stine Maarbjerg","doi":"10.1097/j.pain.0000000000003428","DOIUrl":"10.1097/j.pain.0000000000003428","url":null,"abstract":"<p><strong>Abstract: </strong>There is a limited understanding of risk factors and comorbidities in trigeminal neuralgia, a disease characterized by paroxysms of severe unilateral facial pain and a higher incidence in women. We aim to identify temporally associated comorbidities involving trigeminal neuralgia by analyzing nationwide disease trajectories. Using data from 7.2 million unique individuals in the Danish National Patient Register between 1994 and 2018, each individual diagnosed with trigeminal neuralgia was compared with 10,000 matched controls to identify co-occurring diseases. The sequential disease associations were identified in sex-stratified disease trajectories. A Cox-regression analysis investigated whether treatment with carbamazepine or oxcarbazepine, as compared with gabapentin, pregabalin, or lamotrigine, was associated with stroke risk. Finally, we investigated the stroke polygenic risk score and its association with stroke incidence in a subset of genotyped individuals with trigeminal neuralgia. We included 7141 individuals with trigeminal neuralgia (64.2% female, mean age at diagnosis 58.7 years) and identified 18 diseases associated with subsequent trigeminal neuralgia. After diagnosis, trigeminal neuralgia was associated with 9 diseases, including ischemic stroke (relative risk 1.55). Carbamazepine or oxcarbazepine treatment increased the ischemic stroke risk (hazard ratio 1.78; 95% confidence interval 1.47-2.17); however, the polygenic risk of stroke showed no association. In the Danish population, a trigeminal neuralgia diagnosis is temporally associated with 27 diseases revealed in systematic disease trajectories. Trigeminal neuralgia itself and its first-line treatment, but not a stroke polygenic risk score, was associated with an increased risk of ischemic stroke indicating that vascular risk factors should be routinely assessed in individuals with trigeminal neuralgia.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"879-887"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Child maltreatment elevated the risk of late-life chronic pain: a biopsychosocial framework from the UK Biobank cohort.","authors":"Wenhui Zhao, Xuejing Lu, Yiheng Tu","doi":"10.1097/j.pain.0000000000003417","DOIUrl":"10.1097/j.pain.0000000000003417","url":null,"abstract":"<p><strong>Abstract: </strong>Understanding the development of chronic pain (CP) is challenging due to its multifactorial etiology. Child maltreatment (CM), encompassing various types of neglect and abuse affecting more than one-third of the population, is a critical aspect of early-life adversity with long-lasting impacts. It is increasingly recognized for its role in altering biopsychosocial processes, potentially increasing vulnerability to CP. However, the exact path connecting CM to CP is not fully elucidated, primarily attributable to limitations in prior research, including insufficient sample sizes, inadequate consideration of comprehensive mediative variables, and a lack of longitudinal data. To address these gaps, our study utilizes a large-scale dataset (n = 150,989) comprising both cross-sectional and longitudinal data, along with an extensive range of biopsychosocial variables. Our findings reveal that all types of CMs, except physical neglect, significantly increase the risk of CP, and all types of CPs, except headache, were affected by CM. Furthermore, we demonstrate that individuals with CM histories are more predisposed to comorbid CP conditions. Importantly, biopsychosocial factors are found to explain over 60% of the association between CM and CP, with psychological factors playing a key role. This study not only characterizes the relationship between CM and CP but also underscores the influence of psychosocial elements in this dynamic interplay. These findings offer important insights into the long-term impacts of CM and provide a foundation for developing targeted therapeutic and preventive strategies for CP.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"868-878"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life stress modulates neonatal somatosensation and the transcriptional profile of immature sensory neurons.","authors":"Kyle Harbour, Fady Eid, Elizabeth Serafin, Madailein Hayes, Mark L Baccei","doi":"10.1097/j.pain.0000000000003416","DOIUrl":"10.1097/j.pain.0000000000003416","url":null,"abstract":"<p><strong>Abstract: </strong>Early life stress (ELS) is associated with an increased risk of experiencing chronic pain during adulthood, but surprisingly little is known about the short-term influence of ELS on nociceptive processing in the immature nervous system and the concomitant effects on somatosensation in the neonate. Here, we investigate how ELS modulates pain in neonatal mice and the transcriptional and electrophysiological signatures of immature dorsal root ganglia (DRG). Shortly after the administration of a neonatal limiting bedding (NLB) paradigm from postnatal days (P)2 to P9, both male and female pups exhibited robust hypersensitivity in response to tactile, pressure, and noxious cold stimuli compared with a control group housed under standard conditions, with no change in their sensitivity to noxious heat. Bulk RNA-seq analysis of L3-L5 DRGs at P9 revealed significant alterations in the transcription of pain- and itch-related genes following ELS, highlighted by a marked downregulation in Sst , Nppb , Chrna6 , Trpa1 , and Il31ra . Nonetheless, ex vivo whole-cell patch-clamp recordings from putative A- and C-fiber sensory neurons in the neonatal DRG found no significant changes in their intrinsic membrane excitability following NLB. Overall, these findings suggest that ELS triggers hyperalgesia in neonates across multiple pain modalities that is accompanied by transcriptional plasticity within developing sensory neurons. A better understanding of the mechanisms governing the interactions between chronic stress and pain during the neonatal period could inform the future development of novel interventional strategies to relieve pain in infants and children who have experienced trauma.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":"166 4","pages":"888-901"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Slack potassium channels in spinal dorsal horn neurons control neuropathic pain and acute itch.","authors":"Fangyuan Zhou, Patrick Engel, Peter Ruth, Robert Lukowski, Achim Schmidtko, Ruirui Lu","doi":"10.1097/j.pain.0000000000003427","DOIUrl":"10.1097/j.pain.0000000000003427","url":null,"abstract":"<p><strong>Abstract: </strong>The sodium-activated potassium channel Slack (K Na 1.1, Kcnt1) plays a critical role in tuning neuronal excitability. Previous studies have revealed that Slack is expressed in neurons of the superficial dorsal horn of the spinal cord. However, the precise role of Slack in spinal dorsal horn neurons is unclear. In this study, we used mice in which Slack is conditionally ablated in spinal dorsal horn neurons (Lbx1-Slack -/- mice) and analyzed their behaviors in various models of pain and itch. Lbx1-Slack -/- mice exhibited increased neuropathic pain behavior after peripheral nerve injury but normal responses in a model of inflammatory pain. Unexpectedly, Lbx1-Slack -/- mice demonstrated increased scratching after intradermal injection of chloroquine, LY344864, and histamine. Moreover, neuromedin B receptors are coexpressed with Slack in the dorsal horn, and scratching after intrathecal delivery of neuromedin B was increased in Lbx1-Slack -/- mice. Our study provides in vivo evidence that Slack expressed in spinal dorsal horn neurons inhibits nerve injury-induced allodynia and acute itch induced by various pruritogens.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"858-867"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142392399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatigue, sleep disturbance, and pain interference in children and adolescents with chronic pain: a longitudinal study.","authors":"Josep Roman-Juan, Guillermo Ceniza-Bordallo, Elisabet Sánchez-Rodríguez, Mark P Jensen, Jordi Miró","doi":"10.1097/j.pain.0000000000003432","DOIUrl":"10.1097/j.pain.0000000000003432","url":null,"abstract":"<p><strong>Abstract: </strong>Research has shown that pain and sleep disturbance often co-occur and influence each other over time in children and adolescents with chronic pain. Longitudinal studies examining the underlying mechanisms of this association are scarce and have focused primarily on the role of internalizing mental health symptoms and mood. This longitudinal study aimed to determine whether fatigue underlies the co-occurrence and mutual maintenance of sleep disturbance and pain over time in children and adolescents with chronic pain. Participants were 355 school-aged children and adolescents (mean age = 11.63 year old; 67% female) with chronic pain. The participants provided sociodemographic information and responded a survey that included measures of pain (duration, intensity, interference), sleep disturbance, and fatigue at first assessment and 12 months later. Partially latent, cross-lagged, panel, structural equation models revealed that sleep disturbance, pain intensity, and pain interference co-occurred at both time points. Higher levels of sleep disturbance, pain intensity, and pain interference at first assessment predicted higher levels of sleep disturbance, pain intensity, and pain interference at follow-up, respectively. Higher levels of pain interference at first assessment predicted higher levels of sleep disturbance at follow-up while controlling for initial levels of sleep disturbance. Furthermore, fatigue was found to mediate the association between first assessment and follow-up sleep disturbance, the association between first assessment and follow-up pain interference, and the association between first assessment pain interference and follow-up sleep disturbance. The findings highlight the need to assess and address fatigue in children and adolescents with chronic pain and sleep disturbance.</p>","PeriodicalId":19921,"journal":{"name":"PAIN®","volume":" ","pages":"927-935"},"PeriodicalIF":5.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142546664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}